US9168232B2 - Transdermally absorbable preparation - Google Patents

Transdermally absorbable preparation Download PDF

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Publication number
US9168232B2
US9168232B2 US13/394,656 US201013394656A US9168232B2 US 9168232 B2 US9168232 B2 US 9168232B2 US 201013394656 A US201013394656 A US 201013394656A US 9168232 B2 US9168232 B2 US 9168232B2
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Prior art keywords
acid
transdermally absorbable
absorbable preparation
adhesive layer
acrylic copolymer
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US13/394,656
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US20120226245A1 (en
Inventor
Naohisa Kawamura
Chie Sugaya
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Nipro Patch Co Ltd
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Nipro Patch Co Ltd
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Assigned to NIPRO PATCH CO., LTD. reassignment NIPRO PATCH CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: KAWAMURA, NAOHISA, SUGAYA, CHIE
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465—Nicotine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M35/00—Devices for applying media, e.g. remedies, on the human body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34—Tobacco-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive bandages or dressings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive bandages or dressings
    • A61F13/023—Adhesive bandages or dressings wound covering film layers without a fluid retention layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive bandages or dressings
    • A61F13/0246—Adhesive bandages or dressings characterised by the skin-adhering layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive bandages or dressings
    • A61F13/0246—Adhesive bandages or dressings characterised by the skin-adhering layer
    • A61F13/0253—Adhesive bandages or dressings characterised by the skin-adhering layer characterized by the adhesive material

Definitions

  • the present invention relates to a transdermally absorbable preparation, and more specifically relates to a transdermally absorbable preparation which has on one surface of a backing an adhesive layer containing at least an adhesive agent, and which is used by applying to the skin.
  • transdermally absorbable preparations that administer a drug through the skin surface into a living body have been proposed that have a tape or sheet shape in which an adhesive layer containing a medicinal component is formed on one surface of a nonwoven fabric or plastic film.
  • the type of transdermally absorbable preparation which is applied to the skin requires properties of maintaining a given level of blood concentration over a long time by containing a sufficient amount of a medicinal component in an adhesive layer.
  • Patent Document 1 proposes a type of cross-linking adhesive agent for the skin in which a copolymer A which comprises a (meth)acrylic acid alkyl ester as a main constituent and is copolymerized with diacetone acrylamide, and a copolymer B which comprises a (meth)acrylic acid alkyl ester as a main constituent and comprises a primary amino group and/or a carboxyhydrazide group on side chains are mixed and cross-linked.
  • a copolymer A which comprises a (meth)acrylic acid alkyl ester as a main constituent and is copolymerized with diacetone acrylamide
  • a copolymer B which comprises a (meth)acrylic acid alkyl ester as a main constituent and comprises a primary amino group and/or a carboxyhydrazide group on side chains are mixed and cross-linked.
  • Patent Document 1 Japanese Patent Application Laid-Open No. 2005-325101
  • cross-linking adhesive agent as described in Patent Document 1 is preferably used as an adhesive agent for a transdermally absorbable preparation since a medicinal component and the like can be retained in a network structure formed throughout the entire adhesive agent by cross-linking.
  • the adhesive agent described in Patent Document 1 acquires the above network structure, as well as cohesion (hardness) required as an adhesive agent for a transdermally absorbable preparation since, by mixing the copolymer A and the copolymer B, they are cross-linked with each other to increase cross-linking degree. Since the cross-linking reaction proceeds with time, the cross-linking degree of an adhesive agent is not adequate and quality thereof is not stable for a while after mixing the copolymer A and the copolymer B. Thus, the step of leaving a transdermally absorbable preparation to be produced at, for example, room temperature, i.e.
  • aging is required until the cross-linking degree of the adhesive agent becomes adequate and the quality as a transdermally absorbable preparation becomes stable.
  • the aging requires for several days and is one of the factors that decreases the production rate (throughput) when a transdermally absorbable preparation using an adhesive agent as described above is produced.
  • Such tendency is strengthened when a basic drug is used as a medicinal component.
  • the present invention was made in view of the above situations, and an object thereof is to provide a transdermally absorbable preparation, in which an adhesive agent produced by cross-linking one or more copolymers is contained in an adhesive layer and in which the aging period in producing the adhesive layer can be shortened.
  • the present inventors found that the aging period can be shortened, even when using a basic drug as a medicinal component, by, unexpectedly, coexisting an organic acid when an acrylic copolymer (A) which comprises a (meth)acrylic acid alkyl ester as a main monomer component and which is copolymerized with diacetone acrylamide, and an acrylic copolymer (B) which comprises a (meth)acrylic acid alkyl ester as a main monomer component and which comprises a primary amino group and/or a carboxyhydrazide group on side chains are mixed and they are cross-linked to each other.
  • A acrylic copolymer
  • B which comprises a (meth)acrylic acid alkyl ester as a main monomer component and which comprises a primary amino group and/or a carboxyhydrazide group on side chains
  • the present inventors also found that the aging period when using a basic drug as a medicinal component can be shortened by coexisting an organic acid when the above acrylic copolymer (A) is cross-linked with a polyamine compound such as adipic acid dihydrazide.
  • the present invention is completed based on the knowledge.
  • the present invention is (1) a transdermally absorbable preparation having a backing and an adhesive layer which is placed on the backing and which contains an adhesive agent and a medicinal component, the transdermally absorbable preparation being characterized in that the adhesive agent comprises a resin mixture comprising 100 parts by mass of an acrylic copolymer (A) described below and 0.1 to 30 parts by mass of an acrylic copolymer (B) described below or 0.05 to 2 parts by mass of a polyamine compound and that the adhesive layer further comprises an organic acid.
  • the adhesive agent comprises a resin mixture comprising 100 parts by mass of an acrylic copolymer (A) described below and 0.1 to 30 parts by mass of an acrylic copolymer (B) described below or 0.05 to 2 parts by mass of a polyamine compound
  • the adhesive layer further comprises an organic acid.
  • Acrylic copolymer (A) an acrylic copolymer which comprises a (meth)acrylic acid alkyl ester as a main monomer component, and comprises 3 to 45% by mass of diacetone acrylamide as a prerequisite monomer component, but does not comprise a free carboxyl group.
  • Acrylic copolymer (B) an acrylic copolymer which comprises a (meth)acrylic acid alkyl ester as a main monomer component, and comprises a primary amino group and/or a carboxyhydrazide group on side chains, but does not comprise a free carboxyl group.
  • the present invention is (2) the transdermally absorbable preparation described in (1), comprising as the organic acid at least any of lactic acid, salicylic acid, succinic acid, thioglycolic acid, maleic acid, malonic acid, adipic acid, benzoic acid, capric acid, sorbic acid, malic acid, citric acid, tartaric acid, palmitic acid, fumaric acid, propionic acid, behenic acid, myristic acid and hydrates thereof.
  • the present invention is also (3) the transdermally absorbable preparation described in (1) or (2), wherein the medicinal component is nicotine or lidocaine, or salts thereof.
  • the present invention is (4) the transdermally absorbable preparation described in (3), wherein the medicinal component is nicotine or a salt thereof.
  • the present invention is (5) the transdermally absorbable preparation described in any one of (1) to (4), wherein the adhesive layer further comprises an antioxidant.
  • the present invention is (6) the transdermally absorbable preparation described in (5), wherein the antioxidant is dibutylhydroxytoluene.
  • the present invention is (7) the transdermally absorbable preparation described in any one of (1) to (6), further comprising a patching layer which provide a patching property for the skin, or sequentially comprising a controlled-release membrane which controls release of the medicinal component from the adhesive layer and a patching layer which provides the patching property for the skin on a surface of the adhesive layer.
  • transdermally absorbable preparation in which an adhesive agent produced by cross-linking one or more copolymers is contained in an adhesive layer, and in which the aging period in producing the adhesive layer can be shortened.
  • the transdermally absorbable preparation of the present embodiment has a medicated surface on a backing, and is designed so that the active ingredient will be absorbed through the skin into a body, when the transdermally absorbable preparation is applied to bring the medicated surface into contact with the skin.
  • Such preparations may include those designed to deliver an active ingredient into the systemic blood circulation through the skin, and those designed to topically deliver an active ingredient through the skin.
  • the former is classified into “transdermal systems” in Japanese Pharmacopoeia, whereas the latter is classified into “patches” in Japanese Pharmacopoeia, and the transdermally absorbable preparation of the present invention may be of any of these types.
  • the transdermally absorbable preparation of the present embodiment has on one surface of a backing at least an adhesive layer.
  • a medicinal component is added, and the surface to be in contact with the skin of the adhesive layer corresponds to the medicated surface.
  • the adhesive layer is a layer for providing a patching property of bonding a transdermally absorbable preparation to the skin.
  • the adhesive layer contains a medicinal component, and the medicinal component is absorbed into the skin from the adhesive layer through the medicated surface.
  • the adhesive layer contains an adhesive agent, a medicinal component, an organic acid and, as needed, other components. Among these, the medicinal component is described below, and the adhesive agent, the organic acid and other components will be explained here.
  • the adhesive agent in the present embodiment comprises a resin mixture comprising 100 parts by mass of an acrylic copolymer (A) and 0.1 to 30 parts by mass of an acrylic copolymer (B), which are described below.
  • a network structure can be formed by cross-linking the acrylic copolymer (A) and acrylic copolymer (B).
  • the transdermally absorbable preparation of the present embodiment can contain sufficient amounts of a medicinal component and the like by retaining the medicinal component and the like in the network structure. Therefore, the transdermally absorbable preparation of the present embodiment can maintain a blood concentration of an active ingredient at a given level for a long period of time.
  • the above acrylic copolymer (A) and acrylic copolymer (B) are acrylic resin which does not substantially comprise a free carboxyl group.
  • a decline in transdermal absorbency which accompanies the reaction and bonding of the medicinal component with adhesive agent ingredients (acrylic copolymers) can be prevented.
  • the phrase “not substantially comprise a free carboxyl group” means that all carboxyl groups are converted into substituents such as an ester bond in design terms. Of these, for example, a case where only a few ester bonds and the like are converted into free carboxyl groups by hydrolysis and a case where free carboxyl groups are contained as impurities derived from primary materials may be also contained.
  • the acrylic copolymer (A) contained in the above resin mixture is an acrylic copolymer which comprises a (meth)acrylic acid alkyl ester as a main monomer component, and 3 to 45% by mass of diacetone acrylamide as a prerequisite monomer component.
  • the acryl copolymer (B) contained in the above resin mixture is also an acrylic copolymer which comprises a (meth)acrylic acid alkyl ester as a main monomer component, and a primary amino group and/or a carboxyhydrazide group on side chains.
  • a fine network structure based on the cross-linking reaction of a carbonyl group derived from diacetone acrylamide contained in an acrylic copolymer (A) and a primary amino group and a carboxyhydrazide group contained in an acrylic copolymer (B) can be formed throughout the entire adhesive layer, and a medicinal component and the like can be retained in such network structure.
  • the resin mixture can be preferably used for the adhesive layer of the transdermally absorbable preparation.
  • An example of production of an acrylic copolymer (A) includes a method in which to a (meth)acrylic acid alkyl ester, a main monomer component, diacetone acrylamide, also a monomer component, is added to be 3 to 45% by mass per the total monomers and the obtained mixture is radically polymerized.
  • These monomer components can be polymerized according to a conventional method using a polymerization initiator such as a peroxidized compound or an azo compound.
  • a solvent be appropriately added to adjust the viscosity of the reaction solution.
  • (meth)acrylic acid alkyl esters a (meth)acrylic acid alkyl ester in which alkyl group thereof has 1 to 12 carbon atoms is preferably used. Specific examples include methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, octyl (meth)acrylate, dodecyl (meth)acrylate and the like. These (meth)acrylic acid alkyl esters may be used individually or two or more of the esters may be used in combination.
  • a number average molecular weight thereof is preferably 100,000 to 1,500,000 and a weight average molecular weight thereof is preferably 300,000 to 2,500,000.
  • a molecular weight of an acrylic copolymer (A) within the above range is preferred because an adhesive layer of a transdermally absorbable preparation shows suitable adhesion to the skin.
  • the number average molecular weight of an acrylic copolymer (A) is more preferably 300,000 to 1,000,000 and most preferably 500,000 to 800,000.
  • the weight average molecular weight of an acrylic copolymer (A) is more preferably 500,000 to 2,000,000 and most preferably 1,000,000 to 1,500,000.
  • An example of production of an acrylic copolymer (B) includes a method in which to a (meth)acrylic acid alkyl ester, a main monomer component, a monomer component to introduce a primary amino group and/or a monomer component to introduce a carboxyhydrazide group are added to be 1 to 30% by mass per the total monomers and the obtained mixture is radically polymerized, and then side chains derived from the monomer components to introduce a carboxyhydrazide group are converted into carboxyhydrazide groups.
  • the radical polymerization of the monomer components can be carried out according to a conventional method using a polymerization initiator such as a peroxidized compound or an azo compound.
  • a solvent be appropriately added to adjust the viscosity of the reaction solution.
  • a (meth)acrylic acid alkyl ester used in producing an acrylic copolymer (B) the same as exemplified in the above acrylic copolymer (A) can be used.
  • the number of primary amino group and/or carboxyhydrazide group in an acrylic copolymer (B) is preferably two or more, and more preferably three or more in a molecular chain of the acrylic copolymer (B) for showing suitable crosslinkability with an acrylic copolymer (A).
  • a monomer component to introduce a primary amino group and/or a monomer component to introduce a carboxyhydrazide group, and a (meth)acrylic acid alkyl ester monomer be mixed to have the molar ratio of 1:5 to 1:100 and be copolymerized.
  • a monomer component to introduce a primary amino group into an acrylic copolymer (B) includes a compound having a vinyl group capable of polymerizing with a (meth)acrylic acid alkyl ester, and a primary amino group. Examples of such compound include vinylamine and the like.
  • a monomer component to introduce a carboxyhydrazide group into an acrylic copolymer (B) includes a compound having a vinyl group capable of polymerizing with a (meth)acrylic acid alkyl ester and a keto group capable of reacting with a hydrazide compound.
  • Examples of such compound include diacetone acrylamide, acrolein, acetoacetoxyethyl methacrylate and the like.
  • the polymer obtained by the above radical polymerization is dissolved in a polar solvent, and the obtained solution may be reacted with a dihydrazide of a dicarboxylic acid in the presence of an acid catalyst.
  • dihydrazides of dicarboxylic acids include adipic acid dihydrazide, glutaric acid dihydrazide, pimelic acid dihydrazide and the like.
  • a number average molecular weight thereof is preferably 1,500 to 50,000 and a weight average molecular weight thereof is preferably 2,000 to 100,000.
  • a molecular weight of an acrylic copolymer (B) which is not less than the above lower limit is preferred because gelation of a mixed liquid is inhibited and a coating property becomes good in producing an adhesive layer.
  • a molecular weight of an acrylic copolymer (B) which is not more than the above upper limit is preferred because a suitable cross-linking state with an acrylic copolymer (A) can be obtained.
  • the number average molecular weight of an acrylic copolymer (B) is more preferably 2,000 to 10,000 and most preferably 3,000 to 8,000.
  • the weight average molecular weight of an acrylic copolymer (B) is more preferably 5,000 to 20,000 and most preferably 8,000 to 15,000.
  • the adhesive layer of the transdermally absorbable preparation of the present embodiment can contain an adhesive agent other than the above resin mixture for the purpose, for example, of improving a patching property to the skin and the like.
  • An organic acid used in the present embodiment is contained in the adhesive layer, and has an action to promote cross-linking of an acrylic copolymer (A) and an acrylic copolymer (B).
  • A acrylic copolymer
  • B acrylic copolymer
  • A acrylic copolymer
  • B acrylic copolymer
  • the adhesive layer requires a aging period until the adhesive layer acquires necessary cohesion (hardness) by progression of cross-linking.
  • the present inventors have regarded a long aging period, particularly when using a basic drug as a medicinal component, as a problem, and have explored a method capable of shortening the aging period.
  • the present inventors found that, even when using a basic drug as a medicinal component, by, unexpectedly, further adding an organic acid to a mixture of an acrylic copolymer (A) and an acrylic copolymer (B), the cross-linking reaction of the acrylic copolymer (A) and the acrylic copolymer (B) is promoted and the aging period can be considerably shortened.
  • the present invention is completed based on the knowledge.
  • An organic acid is added to a mixture of an acrylic copolymer (A) and an acrylic copolymer (B).
  • An example method of adding an organic acid includes a method in which the acrylic copolymer (A) and the acrylic copolymer (B) are dissolved in a solvent to produce a mixed solution, and an organic acid, a medicinal component and the like described below are further dissolved in the mixed solution, followed by applying the obtained solution to a backing, and then the solvent contained in the mixed solution applied is evaporated to form the adhesive layer.
  • the amount of the mixed solution to be applied to the backing can be appropriately determined to obtain a desired thickness of the adhesive layer after evaporating the solvent.
  • the cross-linking reaction of the acrylic copolymer (A) and the acrylic copolymer (B) contained in the adhesive layer is initiated, and aging may be carried out until the adhesive layer acquires sufficient cohesion by progression of the cross-linking reaction.
  • cohesion represents hardness of the adhesive layer. Low cohesion may lead to problems that a transdermally absorbable preparation is spontaneously released when it is applied to the skin, and the adhesive layer remains on the skin when the transdermally absorbable preparation is released.
  • Examples of the organic acid used for the transdermally absorbable preparation of the present embodiment include lactic acid, salicylic acid, succinic acid, thioglycolic acid, maleic acid, malonic acid, adipic acid, benzoic acid, capric acid, sorbic acid, malic acid, citric acid, tartaric acid, palmitic acid, fumaric acid, propionic acid, behenic acid, myristic acid and hydrates thereof, and the like.
  • lactic acid is most preferably used.
  • an organic acid is used in the present invention because an inorganic acid has an exceedingly limited effect to promote the cross-linking reaction of an acrylic copolymer (A) and an acrylic copolymer (B).
  • the amount of an organic acid to be used is preferably 0.05 to 5% by mass, more preferably 0.1 to 2% by mass and most preferably 0.3 to 1% by mass per the total mass of an adhesive layer.
  • the amount of an organic acid to be used is 0.05% by mass or more per the total mass of an adhesive layer, the cross-linking reaction of an acrylic copolymer (A) and an acrylic copolymer (B) can be successfully promoted.
  • the amount of an organic acid to be used is 5% by mass or less per the total mass of an adhesive layer, skin irritation caused by applying a transdermally absorbable preparation to the skin can be relieved.
  • additives which are added to an adhesive layer, as needed, to provide a variety of functions for a transdermally absorbable preparation.
  • additives include plasticizers, antioxidants, solvents for dissolving a medicinal component, a variety of adhesive agents, antiseptic agents, pH adjusting agents, chelating agents, transdermal absorption promoters, excipients, flavors, coloring materials and the like.
  • an oily material having a high boiling point may be generally used.
  • the plasticizer include fatty acid ester derivatives such as isopropyl myristate, diethyl sebacate, diisopropyl adipate, ethyl oleate, isopropyl palmitate, ethyl laurate, octyl palmitate, isotridecyl myristate and medium chain fatty acid triglyceride; higher alcohol derivatives such as hexyl decanol and octyl dodecanol; polyalkylene glycols such as polyethylene glycol and polypropylene glycol; fats and oils such as olive oil and castor oil, and the like.
  • isopropyl myristate, isopropyl palmitate and the like are preferred due to not only acting as a plasticizer of an adhesive agent but also having effects of promoting diffusion of a medicinal component in a transdermally absorbable preparation and promoting skin penetration of a medicinal component.
  • the amount of a plasticizer to be added is preferably 1 to 40% by mass, more preferably 5 to 35% by mass, and most preferably 6 to 30% by mass per the total mass of an adhesive layer.
  • a good transdermally absorbable preparation can be obtained without using a plasticizer.
  • a plasticizer may not necessarily used.
  • An antioxidant inhibits oxidation of components contained in an adhesive layer, and a coloration phenomenon of the adhesive layer (a medicated surface) observed when storing a transdermally absorbable preparation for a long period of time is reduced.
  • the preservation stability of a transdermally absorbable preparation can be improved.
  • antioxidants include phenol antioxidants such as dibutylhydroxytoluene (BHT, IUPAC name: 2,6-bis(1,1-dimethylethyl)-4-methylphenol) and dibutylated hydroxyanisole (BHA); ascorbic acid, tocopherol, tocopherol ester derivatives, 2-mercaptobenzimidazole and the like.
  • BHT dibutylhydroxytoluene
  • the amount of an antioxidant to be used is preferably 0.1 to 20% by mass and more preferably 0.5 to 10% by mass per the total mass of an adhesive layer.
  • a solvent for dissolving a medicinal component is not particularly limited as long as it dissolves a drug, and is preferably a solvent which does not cause skin irritation.
  • examples of such solvent include lower alcohols such as ethanol, propanol and isopropanol; medium alcohols such as hexanol and octanol; polyalcohols such as glycerin, ethylene glycol and diethylene glycol; fatty acid esters, polyvinyl alcohols, N-methylpyrrolidone, lactic acid, and the like. These can be used individually or two or more of them can be used in combination.
  • an example of forming an adhesive layer in the transdermally absorbable preparation of the present embodiment includes a method in which components to be contained in the adhesive layer such as the above resin mixture, an organic acid, a medicinal component and the like are dissolved in a solvent to produce a solution, and the solvent contained in the solution is heated and evaporated by a known method.
  • the solvent to be used in such method is not particularly limited as long as it is an organic solvent which is evaporated during the step of drying by heating in production of a transdermally absorbable preparation.
  • Examples thereof can include organic solvents, e.g., ketones such as acetone and methyl ethyl ketone; acetic acid esters such as methyl acetate, ethyl acetate, propyl acetate and butyl acetate; aliphatic hydrocarbons such as hexane, heptane, octane and cyclohexane; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as isopropyl ether, tetrahydrofuran and dioxane; and the like. These can be used individually or two or more of them can be used in combination.
  • ketones such as acetone and methyl ethyl ketone
  • acetic acid esters such as methyl acetate, ethyl acetate, propyl acetate and butyl acetate
  • aliphatic hydrocarbons such as hexane, h
  • a medicinal component used in the transdermally absorbable preparation of the present embodiment is contained in the adhesive layer, and is absorbed into the skin through a medicated surface corresponding to a surface of the adhesive layer and a contact surface with the skin.
  • a kind of medicinal component used in the transdermally absorbable preparation of the present embodiment is not particularly limited. As described herein, when using a basic drug as a medicinal component, the progression of the cross-linking reaction of an acrylic copolymer (A) and an acrylic copolymer (B), which are adhesive agents, is delayed. Thus, there is a tendency to prolong the aging period in producing a transdermally absorbable preparation. From this standpoint, the effect of promoting the cross-linking reaction by adding the above organic acid will be further produced when using a basic drug as a medicinal component.
  • the medicinal component examples include smoking-cessation aids such as nicotine; regional anesthetics such as lidocaine hydrochloride, procaine hydrochloride and lidocaine; narcotic analgesics such as morphine sulfate, fentanyl citrate and fentanyl; antidementia drugs such as donepezil hydrochloride; dysuria improving drugs such as tamsulosin hydrochloride; sedative-hypnotic drugs such as flurazepam hydrochloride and rilmazafone hydrochloride; anti-inflammatory analgesic agents such as butorphanol tartrate and perisoxal citrate; psychostimulants such as methamphetamine hydrochloride and methylphenidate hydrochloride; psychoneurotic agents such as chlorpromazine hydrochloride, imipramine hydrochloride, risperidone, aripiprazole and olanzapine; skeletal muscle relaxants such
  • the above medicinal components can be used in a free base form and in a pharmaceutically acceptable acid addition salt form, and the both forms can be used in combination.
  • an acid addition salt of a basic drug aqueous solution thereof may show neutral to acid due to an acid to be added, such acid addition salt is also called a basic drug in the present invention.
  • the amount of the above medicinal component to be used is preferably 1 to 60% by mass per the total mass of an adhesive layer in terms of preparation physicality and transdermal drug absorbability.
  • the above medicinal components can be used individually or two or more of them can be used in combination.
  • a backing is impermeable or poorly permeable to a medicinal component, and is flexible.
  • films of resin such as polyethylene, polypropylene, an ethylene-vinyl acetate copolymer, an ethylene-vinyl acetate-carbon monoxide copolymer, an ethylene-butyl acrylate-carbon monoxide copolymer, nylon, polyester (polyethylene terephthalate), polybutylene terephthalate and the like, as well as aluminum sheets, and the like.
  • resin such as polyethylene, polypropylene, an ethylene-vinyl acetate copolymer, an ethylene-vinyl acetate-carbon monoxide copolymer, an ethylene-butyl acrylate-carbon monoxide copolymer, nylon, polyester (polyethylene terephthalate), polybutylene terephthalate and the like, as well as aluminum sheets, and the like.
  • These may be laminated and processed into a sheet, or may be laminated together with
  • a surface of a backing may be subjected to surface treatment such as corona treatment, plasma discharge treatment and the like, and subjected to anchor coating treatment with an anchor agent.
  • the transdermally absorbable preparation of the present embodiment differs from the above first embodiment in using as an adhesive agent a resin mixture comprising 100 parts by mass of the above acrylic copolymer (A) and 0.05 to 2 parts by mass of a polyamine compound, and the rest is the same as the above first embodiment.
  • a resin mixture comprising 100 parts by mass of the above acrylic copolymer (A) and 0.05 to 2 parts by mass of a polyamine compound, and the rest is the same as the above first embodiment.
  • the polyamine compound will be described in the following description.
  • the polyamine compound used in the present embodiment is a low molecular compound.
  • a low molecular compound means a monomolecular compound not forming a polymer or an oligomer by polymerization.
  • a polyamine compound is a compound having two or more amino groups in a molecule.
  • an acrylic copolymer (A) is a copolymer produced by polymerizing diacetone acrylamide as a prerequisite monomer, and comprises a keto group derived from diacetone acrylamide in the molecule.
  • a polyamine compound is cross-linked with an acrylic copolymer (A) by reacting the keto group and an amino group contained in the polyamine compound.
  • Example of the polyamine compound most simply include hydrazine or a hydrazine hydrate compound.
  • the amino groups contained in a polyamine compound are preferably bonded to other nitrogen atoms.
  • examples of such compounds include polyhydrazide compounds obtained by acting a hydrazine compound to a polybasic organic acid.
  • Preferred examples of the polyhydrazide compound include dihydrazides of dicarboxylic acids.
  • examples of such compounds include phthalic acid dihydrazide, isophthalic acid dihydrazide, terephthalic acid dihydrazide, oxalic acid dihydrazide, sebacic acid dihydrazide, adipic acid dihydrazide and the like.
  • Particularly preferred polyhydrazide compounds include saturated aliphatic dicarboxylic acids, among these, dihydrazides of saturated aliphatic dicarboxylic acids having 2 to 10 carbon atoms. Examples of such compounds include oxalic acid dihydrazide, sebacic acid dihydrazide and adipic acid dihydrazide. Among these, preferred is adipic acid dihydrazide. Adipic acid dihydrazide is also called adipic acid diamine or adipohydrazide.
  • the above polyamine compound is mixed with an acrylic copolymer (A) to be a resin mixture, which is an adhesive agent.
  • the amount of a polyamine compound to be added is 0.05 to 2 parts by mass and more preferably 0.1 to 1 part by mass per 100 parts by mass of an acrylic copolymer (A).
  • the amount of a polyamine compound to be added is 0.05 parts by mass or more per 100 parts by mass of an acrylic copolymer (A)
  • the acrylic copolymer (A) can be successfully cross-linked and an adhesive agent having appropriate cohesion can be obtained.
  • the amount of a polyamine compound to be added is 2 parts by mass or less per 100 parts by mass of an acrylic copolymer (A)
  • gelation of the acrylic copolymer (A) can be inhibited.
  • the above resin mixture, as well as a medicinal component, an organic acid and, as needed, other components are dissolved in a solvent to prepare a solution, and the solution is applied to a surface of a base to form an adhesive layer on the surface of the base.
  • the procedure is the same as in the description of the first embodiment, and is abbreviated here.
  • the adhesive layer also contains an organic acid.
  • the cross-linking reaction of an acrylic copolymer (A) and an acrylic copolymer (B) as described above although the cross-linking reaction of an acrylic copolymer (A) with a polyamine compound in the present embodiment may be delayed when using a basic drug as a medicinal component, the delay is inhibited due to containing an organic acid in the adhesive layer.
  • the aging period after producing a transdermally absorbable preparation can be shortened and the production rate in producing a transdermally absorbable preparation can be improved.
  • the transdermally absorbable preparation of the present embodiment has an “adhesive layer” described in the first and the second embodiments as a drug retaining layer.
  • the transdermally absorbable preparation of the present embodiment has as a contact surface with the skin a “patching layer” to attach the transdermally absorbable preparation on the skin and to absorb a medicinal component contained in the transdermally absorbable preparation into the skin.
  • a controlled-release membrane is set up, as needed, between the above drug retaining layer and patching layer.
  • the transdermally absorbable preparation of the present embodiment includes, from the opposite side of the skin to which the transdermally absorbable preparation is applied, a backing, a drug retaining layer, a controlled-release membrane and a patching layer which are sequentially formed, or a backing, a drug retaining layer and a patching layer which are sequentially formed.
  • the drug retaining layer is identical with the “adhesive layer” as described above, and can successfully retain a medicinal component in the inside of a network structure formed by cross-linking.
  • the transdermally absorbable preparation of such embodiment is also included within the scope of the invention because of having a given adhesive layer (a drug retaining layer) on one surface of a backing.
  • the transdermally absorbable preparations of the above first and second embodiments have as a contact surface with the skin an “adhesive layer” having a good patching property to the skin and a drug retaining property.
  • the transdermally absorbable preparations of the first and the second embodiments have a good drug delivery action to the skin, the good drug delivery action may be excessive depending on the kinds of medicinal component.
  • an “adhesive layer” containing a medicinal component is used as the drug retaining layer which does not contact the skin, and a controlled-release membrane to control the delivery rate of a medicinal component from the drug retaining layer is set up, as needed, between the drug retaining layer and a patching layer which is a contact surface with the skin.
  • a transdermally absorbable preparation does not have a controlled-release membrane, the above patching layer controls the delivery rate of a medicinal component from the drug retaining layer.
  • the transdermally absorbable preparation of the present embodiment is preferably used for a medicinal component particularly needed to maintain a stable blood concentration for a long period of time.
  • the drug retaining layer of the present embodiment is identical with the “adhesive layer” described above, and is not described here. Since the “adhesive layer” (i.e. a drug retaining layer) in the present embodiment is not a layer to be directly applied to the skin, a patching property is not essential.
  • a controlled-release membrane is set up between a drug retaining layer and a patching layer, and controls a delivery rate of a medicinal component from the drug retaining layer to the patching layer. By this, the delivery rate of a medicinal component from the transdermally absorbable preparation to the skin is controlled.
  • controlled-release membranes can be used without particular restriction.
  • An example of such controlled-release membrane includes ethylene-vinyl acetate copolymer (EVA) or a polyethylene porous membrane.
  • EVA ethylene-vinyl acetate copolymer
  • a thickness, quality, a hole size to be formed and the like of the membrane can be appropriately determined in view of the desired delivery rate of a medicinal component.
  • a method in which a layer of a controlled-release membrane is set up in the transdermally absorbable preparation is not particularly limited, and an example thereof includes a method in which a controlled-release membrane processed into a sheet is pressingly arranged on an adhesive surface of a drug retaining layer formed on a surface of a backing.
  • a patching layer is set to attach a transdermally absorbable preparation to the skin.
  • the patching layer is a contact surface with the skin in a transdermally absorbable preparation, thus it has a role to deliver a medicinal component to the skin. Further, in the form of not using the above controlled-release membrane, such patching layer has a function to control the drug delivery rate from the drug retaining layer.
  • a material to form a patching layer is not particularly limited as long as it has adhesion, and examples thereof include rubber materials such as polyisobutylene, styrene-isoprene-styrene block copolymer and natural rubber; acrylic materials such as acrylates-octyl acrylate copolymer, 2-ethylhexyl acrylate-2-ethylhexyl methacrylate-dodecyl methacrylate copolymer and 2-ethylhexyl acrylate-diacetone acrylamide-acetoacetoxyethyl methacrylate-methyl methacrylate copolymer; and the like. These materials can be used individually or several materials can be used in combination.
  • a method of forming a patching layer is not particularly limited, and examples thereof include a method in which the above material is dissolved in a suitable solvent and then the solution is applied to a surface of a controlled-release membrane, followed by drying it; a method in which the above material is processed into a sheet and the sheet is then pressingly arranged on a surface of a controlled-release membrane; and the like.
  • a thickness of the patching layer is not particularly limited, and can be appropriately determined in view of properties needed for a transdermally absorbable preparation.
  • a tackifier a plasticizer, an antioxidant, a stabilizer and the like other than the above materials can be added, as needed.
  • transdermally absorbable preparation of the present invention was described by way of specific embodiments.
  • the present invention is not, however, limited to the above embodiments and may be practiced with modification and alteration within the scope of constitution of the present invention.
  • transdermally absorbable preparation of the present invention will now be described in more detail by way of examples thereof. It should be noted, however, that the present invention is not limited to the following examples.
  • a solution of an acrylic copolymer (A) and a solution of an acrylic copolymer (B) obtained according to synthesis methods described below were mixed so that a mass ratio of resin contained in the solution would be 100:5 (acrylic copolymer (A): acrylic copolymer (B)) to produce an adhesive agent (a resin mixture).
  • each one aliquot of the remaining four aliquots was added at one hour intervals after 2 hours from initiation of the polymerization reaction. After completion of the addition, the reaction was carried out for another 2 hours. After initiation of the reaction, 50 parts by mass of ethyl acetate was added four times at 2 hour intervals to adjust viscosity. After completion of the reaction, the reaction mixture was cooled, and ethyl acetate was then added thereto to obtain a solution of the acrylic copolymer (A) with 30% by mass of solid concentration. In the obtained acrylic copolymer (A), the number average molecular weight was about 680,000 and the weight average molecular weight was about 1,200,000.
  • ethyl acrylate To 660 parts by mass of ethyl acrylate, 70 parts by mass of diacetone acrylamide, 40 parts by mass of dodecyl mercaptan as a molecular weight modifier and 400 parts by mass of ethyl acetate were added and mixed. This mixture was transferred into a separable flask equipped with a stirrer and a reflux condenser, and it was heated to 70° C. while stirring and performing nitrogen replacement. A solution in which 5 parts by mass of azobisisobutyronitrile was dissolved in 100 parts by mass of ethyl acetate was divided into five aliquots, and one aliquot was added to the separable flask to initiate a polymerization reaction.
  • the reaction mixture was cooled, and then washed with purified water three times.
  • the obtained product was dissolved in a mixed solvent of 700 parts by mass of ethyl acetate, 1,400 parts by mass of acetone and 400 parts by mass of methanol to obtain a solution of the acrylic copolymer (B) with 30% by mass of solid concentration.
  • the number average molecular weight was about 6,500 and the weight average molecular weight was about 11,000.
  • an adhesive agent a resin mixture obtained in the above production example
  • nicotine a free form
  • a variety of organic acids were added, and the entire solution was stirred uniformly to obtain a mixed liquid.
  • this mixed liquid was applied to a backing, the backing having a coating surface which was subjected to corona treatment and being a PET (polyethylene terephthalate) film of 25 ⁇ m thick, and was dried to form an adhesive layer.
  • the transdermally absorbable preparations of Examples 1 to 11 were produced.
  • the organic acids used in each example are shown in Table 1. Each component was added so that a value of % by mass after drying would be as shown in Table 1. Each value shown in Table 1 means % by mass.
  • the transdermally absorbable preparations of Comparative Examples 1 to 3 were produced by the same procedures as in the above Examples 1 to 11 except that an inorganic acid was added in place of an organic acid or no acid was added. Each component was added so that a value of % by mass after drying would be as shown in Table 2. Each value shown in Table 2 means % by mass.
  • Each transdermally absorbable preparation of Examples 1 to 11 and Comparative Examples 1 to 3 was left at 25° C. after being produced, and time (days) for which the adhesive layer took to acquire cohesion not retaining an adhesive agent on the skin was examined.
  • the time corresponds to the aging period.
  • the shorter time indicates a faster cross-linking rate of the adhesive agent.
  • the transdermally absorbable preparations of Examples 12 to 33 were produced by the same procedures as in the above Examples 1 to 11 except that lidocaine was used as a medicinal component and isopropyl myristate (IPM) was added as a plasticizer.
  • the organic acids used in each Example are shown in Tables 3 and 4. Each component was added so that a value of % by mass after drying would be as shown in Tables 3 and 4. Each value shown in Tables 3 and 4 means % by mass.
  • the transdermally absorbable preparations of Comparative Examples 4 to 6 were produced by the same procedures as in the above Examples 12 to 33 except that an inorganic acid was added in place of an organic acid. Each component was added so that a value of % by mass after drying would be as shown in Table 5. Each value shown in Table 5 means % by mass.
  • transdermally absorbable preparation for test was applied to one surface of the skin, and cumulative amounts of drug permeation were examined by measuring cumulative amounts of nicotine eluted into a receiver through the skin each at 4 hours, 8 hours and 24 hours after the onset of the test. The results are shown in Table 6.
  • the test was performed using the transdermally absorbable preparation of Example 1 and a commercially available nicotine patch (NICODERMTM), and areas of the medicated surfaces of the transdermally absorbable preparations used in the test were 0.95 cm 2 for the transdermally absorbable preparation of Example 1 and 1.77 cm 2 for the commercially available nicotine patch.
  • the transdermally absorbable preparations of Examples 34 to 38 were left at 40° C. for a month, and degree of coloration of an adhesive layer (a medicated surface) from the production of the transdermally absorbable preparations was evaluated by color difference ( ⁇ E).
  • the results are shown in Table 7.
  • chromaticity of a surface of the adhesive layer was measured using a spectrophotometer (Model SP64, manufactured by X-Rite Inc.), and changes in chromaticity of the preparations immediately after being produced and after being left at 40° C. for a month were obtained by calculating using the following formula.
  • the transdermally absorbable preparation of Example 1 has the amount of drug permeation to the skin roughly equivalent to that of a commercially available nicotine patch, thus it is understood that the transdermally absorbable preparation of the present invention can be preferably applied to the use of a nicotine patch.
  • a mixed liquid of 53 parts by mass of the adhesive agent obtained in the above production example (a resin mixture), 42 parts by mass of nicotine (a free form) as a medicinal component, 0.2 parts by mass of lactic acid and 4.8 parts by mass of BHT was produced.
  • the mixed liquid was applied to a nonwoven fabric, the nonwoven fabric being a backing in which unwoven fabric having a basis weight of 12 g/cm 2 was laminated on PET film of 12 ⁇ m thick, and was dried so that a thickness after drying would be 87 ⁇ m to form a drug retaining layer.
  • a porous polyethylene membrane, a controlled-release membrane, (Product Name; CoTran 9719, manufactured by 3M) was pressingly arranged on a surface of the drug retaining layer.
  • the amount of drug permeation of the transdermally absorbable preparation of Example 39 was evaluated by the same method as for the transdermally absorbable preparation of Example 1.
  • a commercially available nicotine patch (NICODERMTM, containing 5.2 mg/cm 2 of nicotine) punched out in the same size as the transdermally absorbable preparation of Example 39 (0.95 cm 2 ) was used as control sample. Consequently, as shown in Table 8, cumulative amounts of nicotine eluted into a receiver at 4 hours, 8 hours and 24 hours from the onset of the test were 198 ⁇ g, 451.9 ⁇ g and 942.8 ⁇ g, respectively, per 1 cm 2 of the transdermally absorbable preparation.
  • the transdermally absorbable preparation has a lower amount of drug than that of a commercially available nicotine patch, however it has the amount of drug permeation to the skin roughly equivalent to that of a commercially available product.
  • the transdermally absorbable preparation of the present invention can be preferably applied to the use of a nicotine patch.

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Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5725940B2 (ja) * 2011-04-01 2015-05-27 日東電工株式会社 ニコチン含有貼付製剤
US20150209302A1 (en) * 2012-09-03 2015-07-30 Nipro Patch Co., Ltd. Adhesive skin patch
US9974858B2 (en) 2015-08-29 2018-05-22 Medrx Co., Ltd Percutaneous absorption composition
WO2017037813A1 (fr) * 2015-08-29 2017-03-09 株式会社メドレックス Composition à absorption par voie cutanée comprenant un médicament basic et un acide sorbique
WO2017061393A1 (fr) * 2015-10-06 2017-04-13 久光製薬株式会社 Patch adhésif
ES2805342T3 (es) * 2015-10-26 2021-02-11 Hisamitsu Pharmaceutical Co Parche cutáneo adhesivo
WO2018052039A1 (fr) 2016-09-16 2018-03-22 ニチバン株式会社 Timbre transdermique
US10898448B2 (en) * 2017-04-25 2021-01-26 Hisamitsu Pharmaceutical Co., Inc. Patch
BR112021001304A2 (pt) * 2019-04-24 2021-11-16 Medrx Co Ltd Preparação de emplastro, e, método para fabricar a preparação de emplastro
US20220047541A1 (en) * 2020-08-17 2022-02-17 Pike Therapeutics, Inc. Pharmaceutical compositions and methods for treating parkinson's disease

Citations (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3387001A (en) * 1964-10-19 1968-06-04 Lilly Co Eli Novel aminoacyl esters of desacetyl vincaleukoblastine
US4166810A (en) * 1978-04-20 1979-09-04 Eli Lilly And Company Derivatives of 4-desacetyl VLB C-3 carboxyhydrazide
US4322351A (en) * 1980-08-25 1982-03-30 Eli Lilly And Company Antineoplastic 4'-formylamino and 4'-acetylamino VLB, and derivatives thereof
JPS61251619A (ja) 1985-04-30 1986-11-08 Nitto Electric Ind Co Ltd ニコチン含有テ−プ製剤
US4667030A (en) * 1985-06-17 1987-05-19 Eli Lilly And Company Hydrazide succinimide derivatives of antineoplastic indole-dihydroindole alkaloids
US4675400A (en) * 1985-06-17 1987-06-23 Eli Lilly And Company Bifunctional derivatives of 4-desacetyl indole-dihydroindole alkaloids
US4751087A (en) * 1985-04-19 1988-06-14 Riker Laboratories, Inc. Transdermal nitroglycerin delivery system
US4801688A (en) * 1986-05-27 1989-01-31 Eli Lilly And Company Hydrazone immunoglobulin conjugates
US4908213A (en) 1989-02-21 1990-03-13 Schering Corporation Transdermal delivery of nicotine
US5043340A (en) * 1990-04-03 1991-08-27 Eli Lilly And Company Derivatives of 4-desacetyl VLB C-3 carboxhydrazide
US5043336A (en) * 1990-04-03 1991-08-27 Eli Lilly And Company Cyclic imide derivatives of 4-desacetyl VLB c-3 carboxhydrazide
JPH0640947A (ja) 1992-07-28 1994-02-15 T T S Gijutsu Kenkyusho:Kk 経皮吸収製剤用組成物および経皮吸収製剤
US5435879A (en) * 1986-05-30 1995-07-25 Rohm And Haas Company Methods of using pressure-sensitive adhesives
US5962012A (en) * 1997-11-28 1999-10-05 Caleb Pharmaceuticals, Inc. Cholinergic antagonist patch
WO2000044846A1 (fr) * 1999-01-29 2000-08-03 Strakan Limited Adhesifs
EP1043020A1 (fr) * 1997-12-25 2000-10-11 Daiichi Pharmaceutical Co., Ltd. Composition medicinale pour administration percutanee
US6284269B1 (en) * 1997-08-27 2001-09-04 Hexal Ag Pharmaceutical compositions of meloxicam with improved solubility and bioavailability
WO2002009653A1 (fr) 2000-07-27 2002-02-07 Strakan Pharmaceuticals Limited Bandes cosmetiques adhesives
US20030113365A1 (en) * 2001-07-09 2003-06-19 3M Innovative Properties Company Pyrrolidonoethyl (meth)acrylate containing pressure sensitive adhesive compositions
US6617387B2 (en) * 2000-08-21 2003-09-09 Basf Aktiengesellschaft Ammonia-free polymer dispersions as additives in mineral building materials based on hydraulic binders
WO2004026313A1 (fr) * 2002-09-17 2004-04-01 Nippon Boehringer Ingelheim Co., Ltd. Composition pharmaceutique pour l'administration topique de meloxicam, qui contient une amine ou un amide comme agent facilitant la penetration
JP2005325101A (ja) 2004-04-13 2005-11-24 Kosumedei:Kk 架橋型皮膚用粘着剤
US20060110433A1 (en) * 2002-08-28 2006-05-25 Takaaki Terahara Adhesive patch
JP2006348219A (ja) 2005-06-17 2006-12-28 Showa Highpolymer Co Ltd 水性樹脂分散体
US20070098766A1 (en) * 2003-06-24 2007-05-03 Saitama Daiichi Pharmaceutical Co., Ltd. Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous asorption, and process for producing the same
JP2007137876A (ja) 2005-10-19 2007-06-07 Saitama Daiichi Seiyaku Kk 貼付剤、及び貼付剤の製造方法
US20070196455A1 (en) * 2004-04-13 2007-08-23 Saitama Daiichi Pharmaceutical Co., Ltd. Crosslinkable pressure-sensitive adhesive for skin
JP2007284378A (ja) 2006-04-17 2007-11-01 Saitama Daiichi Seiyaku Kk 選択的セロトニン再取込阻害成分を含有する製剤
US20080131488A1 (en) * 2004-12-15 2008-06-05 Naohisa Kawamura Medical Tape Preparation
JP2008208084A (ja) 2007-02-27 2008-09-11 Hisamitsu Pharmaceut Co Inc ニコチン徐放性貼付剤
WO2008133982A2 (fr) 2007-04-27 2008-11-06 Lectec Corporation Timbre adhésif contenant un agent aversif
JP2010241784A (ja) 2008-06-19 2010-10-28 Mitsubishi Tanabe Pharma Corp 経皮投与製剤
US7875612B2 (en) * 2001-04-24 2011-01-25 Purdue Research Foundation Folate mimetics and folate-receptor binding conjugates thereof
US8044200B2 (en) * 2005-03-16 2011-10-25 Endocyte, Inc. Synthesis and purification of pteroic acid and conjugates thereof
US8105568B2 (en) * 2003-01-27 2012-01-31 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
US8288557B2 (en) * 2004-07-23 2012-10-16 Endocyte, Inc. Bivalent linkers and conjugates thereof
US8465724B2 (en) * 2005-08-19 2013-06-18 Endocyte, Inc. Multi-drug ligand conjugates

Patent Citations (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3387001A (en) * 1964-10-19 1968-06-04 Lilly Co Eli Novel aminoacyl esters of desacetyl vincaleukoblastine
US4166810A (en) * 1978-04-20 1979-09-04 Eli Lilly And Company Derivatives of 4-desacetyl VLB C-3 carboxyhydrazide
US4322351A (en) * 1980-08-25 1982-03-30 Eli Lilly And Company Antineoplastic 4'-formylamino and 4'-acetylamino VLB, and derivatives thereof
US4751087B1 (fr) * 1985-04-19 1993-03-02 Riker Laboratories Inc
US4751087A (en) * 1985-04-19 1988-06-14 Riker Laboratories, Inc. Transdermal nitroglycerin delivery system
JPS61251619A (ja) 1985-04-30 1986-11-08 Nitto Electric Ind Co Ltd ニコチン含有テ−プ製剤
US4667030A (en) * 1985-06-17 1987-05-19 Eli Lilly And Company Hydrazide succinimide derivatives of antineoplastic indole-dihydroindole alkaloids
US4675400A (en) * 1985-06-17 1987-06-23 Eli Lilly And Company Bifunctional derivatives of 4-desacetyl indole-dihydroindole alkaloids
US4801688A (en) * 1986-05-27 1989-01-31 Eli Lilly And Company Hydrazone immunoglobulin conjugates
US5435879A (en) * 1986-05-30 1995-07-25 Rohm And Haas Company Methods of using pressure-sensitive adhesives
US4908213A (en) 1989-02-21 1990-03-13 Schering Corporation Transdermal delivery of nicotine
JPH04503357A (ja) 1989-02-21 1992-06-18 シェリング・コーポレーション ニコチンの経皮デリバリー用デバイス
US5043336A (en) * 1990-04-03 1991-08-27 Eli Lilly And Company Cyclic imide derivatives of 4-desacetyl VLB c-3 carboxhydrazide
US5043340A (en) * 1990-04-03 1991-08-27 Eli Lilly And Company Derivatives of 4-desacetyl VLB C-3 carboxhydrazide
JPH0640947A (ja) 1992-07-28 1994-02-15 T T S Gijutsu Kenkyusho:Kk 経皮吸収製剤用組成物および経皮吸収製剤
US6284269B1 (en) * 1997-08-27 2001-09-04 Hexal Ag Pharmaceutical compositions of meloxicam with improved solubility and bioavailability
US5962012A (en) * 1997-11-28 1999-10-05 Caleb Pharmaceuticals, Inc. Cholinergic antagonist patch
EP1043020A1 (fr) * 1997-12-25 2000-10-11 Daiichi Pharmaceutical Co., Ltd. Composition medicinale pour administration percutanee
WO2000044846A1 (fr) * 1999-01-29 2000-08-03 Strakan Limited Adhesifs
WO2002009653A1 (fr) 2000-07-27 2002-02-07 Strakan Pharmaceuticals Limited Bandes cosmetiques adhesives
US6617387B2 (en) * 2000-08-21 2003-09-09 Basf Aktiengesellschaft Ammonia-free polymer dispersions as additives in mineral building materials based on hydraulic binders
US7875612B2 (en) * 2001-04-24 2011-01-25 Purdue Research Foundation Folate mimetics and folate-receptor binding conjugates thereof
US20030113365A1 (en) * 2001-07-09 2003-06-19 3M Innovative Properties Company Pyrrolidonoethyl (meth)acrylate containing pressure sensitive adhesive compositions
US20060110433A1 (en) * 2002-08-28 2006-05-25 Takaaki Terahara Adhesive patch
WO2004026313A1 (fr) * 2002-09-17 2004-04-01 Nippon Boehringer Ingelheim Co., Ltd. Composition pharmaceutique pour l'administration topique de meloxicam, qui contient une amine ou un amide comme agent facilitant la penetration
US8105568B2 (en) * 2003-01-27 2012-01-31 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
US20070098766A1 (en) * 2003-06-24 2007-05-03 Saitama Daiichi Pharmaceutical Co., Ltd. Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous asorption, and process for producing the same
JP2005325101A (ja) 2004-04-13 2005-11-24 Kosumedei:Kk 架橋型皮膚用粘着剤
US20070196455A1 (en) * 2004-04-13 2007-08-23 Saitama Daiichi Pharmaceutical Co., Ltd. Crosslinkable pressure-sensitive adhesive for skin
US20100076112A1 (en) * 2004-04-13 2010-03-25 Nipro Patch Co., Ltd. Crosslinkable pressure-sensitive adhesive for skin
US8288557B2 (en) * 2004-07-23 2012-10-16 Endocyte, Inc. Bivalent linkers and conjugates thereof
US20080131488A1 (en) * 2004-12-15 2008-06-05 Naohisa Kawamura Medical Tape Preparation
US8044200B2 (en) * 2005-03-16 2011-10-25 Endocyte, Inc. Synthesis and purification of pteroic acid and conjugates thereof
JP2006348219A (ja) 2005-06-17 2006-12-28 Showa Highpolymer Co Ltd 水性樹脂分散体
US8465724B2 (en) * 2005-08-19 2013-06-18 Endocyte, Inc. Multi-drug ligand conjugates
JP2007137876A (ja) 2005-10-19 2007-06-07 Saitama Daiichi Seiyaku Kk 貼付剤、及び貼付剤の製造方法
JP2007284378A (ja) 2006-04-17 2007-11-01 Saitama Daiichi Seiyaku Kk 選択的セロトニン再取込阻害成分を含有する製剤
JP2008208084A (ja) 2007-02-27 2008-09-11 Hisamitsu Pharmaceut Co Inc ニコチン徐放性貼付剤
WO2008133982A2 (fr) 2007-04-27 2008-11-06 Lectec Corporation Timbre adhésif contenant un agent aversif
JP2010241784A (ja) 2008-06-19 2010-10-28 Mitsubishi Tanabe Pharma Corp 経皮投与製剤

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
Extended European Search Report issued for EP 10813735.7, mailed Apr. 23, 2013.
International Search Report issued for PCT/JP2010/064937, mailed Nov. 30, 2010.
Japanese Notice of Reasons for Rejection corresponding to Patent Application No. 2011-529919; Date of Mailing: Feb. 10, 2015.
Kessel, Nicola et al., "The diacetone acrylamide crosslinking reaction and its influence on the film formation of an acrylic latex", J. Coat. Technol. Res., vol. 5(3), pp. 285-297, 2008.
Morrison, Robert T. and Boyd, Robert N., "Lehrbuch der Organischen Chemie", 2., berichtigte Auflage, Verlag Chemie, Weinheim, 1978, pp. 698-702.
Morriston, R.T., et al., "Addition Reactions of Ammonia Derivatives", Organic Chemistry, 6th Ed., Mar. 1, 1995, pp. 866-867.
Office Action issued to RU Application No. 2012113139, mailed Jul. 23, 2014.

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EP2476414B1 (fr) 2015-03-04
TW201113341A (en) 2011-04-16
TWI502037B (zh) 2015-10-01
EP2476414A1 (fr) 2012-07-18
JPWO2011027786A1 (ja) 2013-02-04
RU2012113139A (ru) 2013-10-20
ES2574032T3 (es) 2016-06-14
US20120226245A1 (en) 2012-09-06

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